Detection of aberrant methylated SEPT9 and NTRK3 genes in sporadic colorectal cancer patients as a potential diagnostic biomarker

Sharif, Shahin Behrouz; Hashemzadeh, Shahryar; Ardehaie, Reza Mousavi; Eftekharsadat, Amirtaher; Ghojazadeh, Morteza; Mehrtash, A.; Estiar, Mehrdad Asghari; Teimoori‐Toolabi, Ladan; Sakhinia, Ebrahim

doi:10.3892/ol.2016.5327

Cited by 25 publications

(11 citation statements)

References 44 publications

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“…Aberrantly methylated genes are common to CRC, and these methylation changes can also be detected in ctDNA . One such ctDNA test is COLVERA, which detects hypermethylated regions within branched‐chain amino acid transaminase 1 ( BCAT1 ) and Ikaros family zinc‐finger 1 protein ( IKZF1 ) .…”

Section: Introductionmentioning

confidence: 99%

Circulating epigenetic biomarkers for detection of recurrent colorectal cancer

Symonds

Pedersen²,

Murray³

et al. 2020

Cancer

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Background The sensitive detection of recurrent colorectal cancer (CRC) by the measurement of circulating tumor DNA (ctDNA) might improve the chance of a cure. This study compared a quantitative methylated ctDNA test with carcinoembryonic antigen (CEA) in the setting of surveillance for recurrence. Methods Blood samples collected either during surveillance or within 12 months of the confirmation of recurrence were assayed for ctDNA (methylated branched‐chain amino acid transaminase 1 [BCAT1]/Ikaros family zinc‐finger 1 protein [IKZF1]) and CEA. The optimal ctDNA threshold was determined by receiver operating characteristic analysis, and the test performance for the detection of recurrence was compared with CEA (5 ng/mL threshold). Results The study cohort comprised 144 eligible patients and included 50 recurrence events. The sensitivity of the methylated ctDNA test for recurrence was 66.0% (95% confidence interval [CI], 57.1%‐69.3%), which was significantly higher than the sensitivity of CEA (31.9%; 95% CI, 22.8%‐36.6%; P < .001). The sensitivity for resectable recurrence (n = 20) was also higher (ctDNA, 60.0%; CEA, 20.0%; P = .01). The specificity did not differ between the tests (ctDNA, 97.9%; 95% CI, 93.2%‐99.6%; CEA, 96.4%; 95% CI, 91.4%‐99.0%). When adjustments were made for other predictors of the presence of recurrence, a positive ctDNA test was an independent predictor (odds ratio, 155.7; 95% CI, 17.9‐1360.6; P < .001), whereas CEA was not (odds ratio, 2.5; 95% CI, 0.3‐20.6; P = .407). Conclusions The quantitative ctDNA test showed superior sensitivity in comparison with CEA without a difference in the specificity for detecting recurrent CRC. Longitudinal studies are warranted to further assess the utility (specifically the survival benefit) of methylated BCAT1/IKZF1 ctDNA in the surveillance of patients with CRC.

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Section: Introductionmentioning

confidence: 99%

Circulating epigenetic biomarkers for detection of recurrent colorectal cancer

Symonds

Pedersen²,

Murray³

et al. 2020

Cancer

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“…While hypermethylation in promoter region of multiple tumor genes could be stably detected in most cancers (>90%), which makes it a feasible and specific biomarker [ 15 ]. Mounting evidence indicate that altered DNA methylation is one of the most common aberrant epigenetic modifications, which play essential roles in CRC initiation and progression [ 16 , 17 ]. Therefore, CRC specifically methylated cell-free DNA in plasma may serve as a putative biomarker for early detection, therapeutic efficacy assessment, and recurrence monitoring.…”

Section: Introductionmentioning

confidence: 99%

Cell-Free Circulating Methylated SEPT9 for Noninvasive Diagnosis and Monitoring of Colorectal Cancer

Peng

Zhang

et al. 2018

Disease Markers

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Identification of early-stage tumor and monitoring therapeutic efficacy and recurrence or metastasis of colorectal cancer (CRC) are urgently warranted for improving the outcome of CRC patients and reducing the disease-related mortality. In this study, we evaluated the diagnostic value of cell-free circulating methylated SEPT9 (mSEPT9) for CRC and beyond CRC and examined the potentiality of mSEPT9 in assessing therapeutic efficacy and monitoring recurrence of CRC. Our results confirmed the favorable diagnostic value of plasma mSEPT9 for CRC, with a sensitivity of 61.22% (95% confidence interval (CI): 51.33%–70.27%) and specificity of 93.7% (95% CI: 91.09%–95.57%) using 2/3 algorithm. The positive rate of mSEPT9 in CRC was correlated with tumor size, histological grade, and general histological type (P < 0.05). Beyond CRC, gastric cancer patients also presented a high positive rate of plasma mSEPT9 (70%). The conversions between preoperative and postoperative plasma mSEPT9 reflected the therapeutic efficacy of curatively intended surgery for CRC patients. The persistent positivity of plasma mSEPT9 after surgery (within 7–14 days) was highly associated with impending recurrences or metastases (within one year), with a sensitivity of 100%. Postoperative mSEPT9 status during follow-up also provided valuable indication for CRC recurrence or metastases, with a good consistency (kappa = 0.818, P = 0.001). Our results verified the reliability of plasma mSEPT9 as a biomarker for noninvasive diagnosis of CRC. More significantly, we revealed its valuable role in appraising CRC therapeutic efficacy and monitoring CRC recurrences or metastases. Further studies with larger sample sizes are needed to verify and elucidate the clinical utility of the promising findings.

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“…Overexpressed ERG variant 2 was found in lung tumors compared to adjacent tissues, which suggested that ERG might exert an oncogenic effect in lung tumors through functions encoded by variant 2 . Aberrantly methylated NTRK3 has been demonstrated to be involved in various cancers including colorectal cancer and lung cancer . Poor survival in lung cancer was closely associated with NTRK3 .…”

Section: Discussionmentioning

confidence: 99%

Identification of nine microRNAs as potential biomarkers for lung adenocarcinoma

et al. 2019

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Lung cancer is a leading global cause of cancer‐related death, and lung adenocarcinoma (LUAD) accounts for ~ 50% of lung cancer. Here, we screened for novel and specific biomarkers of LUAD by searching for differentially expressed mRNAs (DEmRNAs) and microRNAs (DEmiRNAs) in LUAD patient expression data within The Cancer Genome Atlas (TCGA). The identified optimal diagnostic miRNA biomarkers were used to establish classification models (including support vector machine, decision tree, and random forest) to distinguish between LUAD and adjacent tissues. We then predicted the targets of identified optimal diagnostic miRNA biomarkers, functionally annotated these target genes, and performed receiver operating characteristic curve analysis of the respective DEmiRNA biomarkers, their target DEmRNAs, and combinations of DEmiRNA biomarkers. We validated the expression of selected DEmiRNA biomarkers by quantitative real‐time PCR (qRT‐PCR). In all, we identified a total of 13 DEmiRNAs, 2301 DEmRNAs and 232 DEmiRNA–target DEmRNA pairs between LUAD and adjacent tissues and selected nine DEmiRNAs (hsa‐mir‐486‐1, hsa‐mir‐486‐2, hsa‐mir‐153, hsa‐mir‐210, hsa‐mir‐9‐1, hsa‐mir‐9‐2, hsa‐mir‐9‐3, hsa‐mir‐577, and hsa‐mir‐4732) as optimal LUAD‐specific biomarkers with great diagnostic value. The predicted targets of these nine DEmiRNAs were significantly enriched in transcriptional misregulation in cancer and central carbon metabolism. Our qRT‐PCR results were generally consistent with our integrated analysis. In summary, our study identified nine DEmiRNAs that may serve as potential diagnostic biomarkers of LUAD. Functional annotation of their target DEmRNAs may provide information on their roles in LUAD.

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Detection of aberrant methylated SEPT9 and NTRK3 genes in sporadic colorectal cancer patients as a potential diagnostic biomarker

Cited by 25 publications

References 44 publications

Circulating epigenetic biomarkers for detection of recurrent colorectal cancer

Circulating epigenetic biomarkers for detection of recurrent colorectal cancer

Cell-Free Circulating Methylated SEPT9 for Noninvasive Diagnosis and Monitoring of Colorectal Cancer

Identification of nine microRNAs as potential biomarkers for lung adenocarcinoma

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